Project 2 complements studies of osteoporosis pathophysiology (Project 1) and treatment (Project 4) by addressing fractures, the principle clinical manifestation of the condition. Taking advantage of the unique data resources of the Rochester Epidemiology Project for studies of fracture incidence and outcomes in the community, these studies span decades and cannot be done as efficiently anywhere else. Our ability to identify inception cohorts of Rochester residents with various medical and surgical condition is exploited in a series of retrospective (=historical) cohort studies to estimate the risk of age-related fractures associated with secondary osteoporosis, an important contributor to bone loss in the elderly. Previous studies have addressed fracture risk following Alzheimer's disease and stroke. We now propose to undertake the first population-based studies of fracture risk associated with asthma and anorexia nervosa. While asthma anorexia nervosa disproportionately affect the young, impaired peak bone mass may be an early determinant of osteoporosis later in life. These studies will assess the risk of hip and other fractures, relative to age- and sex-matched controls from the community, among Rochester residents with onset of definite asthma in 1964- 83 (n= 1,547) or first diagnosed with anorexia nervosa in 1950-94 (n greater than 200). To better quantify the fracture risk in the elderly which might be attributable to secondary osteoporosis, we plan three interrelated case-control studies made possible by our ability to identify all diagnosed fractures in the community and to randomly sample controls from the general population. Cases will represent inception cohorts of Rochester residents with a first hip fracture in 1980-92 (n greater than 800), a first vertebral fracture in 1980-94 (n greater than 900) or a first distal forearm fracture in 1980-94 (n greater than 950). These large studies will be strictly population-based and feature reliable ascertainment of the key exposures from contemporary medical records which are comparable for cases and controls. They will be the first studies in a natural population to include both genders and all ages, and they will provide data on fracture trends in North America and are important for generating hypotheses about fracture etiology. The additional age-and sex- specific incidence rates for fractures at all skeletal sites among Rochester residents in 1989-91 (n greater than 1,700) will allow us to better estimate the lifetime risk of fractures associated with osteoporosis. Our overall goal is to develop new information that will lead to effective strategies for preventing osteoporosis-related fractures among the elderly.